Lawsone, a 2-hydroxy-1,4-naphthoquinone from Lawsonia inermis (henna), produces mitochondrial dysfunctions and triggers mitophagy in Saccharomyces cerevisiae
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Lawsone is a natural naphthoquinone present in the henna leaf extract with several cytotoxic activities and used as precursor for synthesis of various pharmaceutical compounds. Its biological activities are thought to be the result of oxidative stress generated, although the hydroxy group at position C-2 in its structure tends to reduce its electrophilic potential. In view of lack of knowledge on its activity, the present work aimed to elucidate the biological effect of lawsone using the yeast Saccharomyces cerevisiae. In the model strain BY4741 it was defined 229 mmol/L as the minimal inhibitory concentration (MIC). Using 172 mmol/L as sub-MIC value it was observed that yap1 deletion mutant was sensitive to lawsone independent the presence of oxygen. Lawsone affected yeast growth in glycerol, indicating interference in the respiratory metabolism. Intracellular content of thiol groups did not indicate intensive oxidative stress and the presence of the anti-oxidant N-acetylcysteine (NAC) exacerbated lawsone toxicity. By analysing the sensitivity of atg mutant strains and the localization of GFP-Atg8 fusion protein, it was concluded that lawsone primarily produces mitochondrial malfunctioning, leading to indirect oxidative stress. It triggers the autophagic response that ultimately induces mitophagy.
KeywordsATG genes Henna Mitochondrial dysfunction Oxidative stress Thiols
The authors are grateful to Prof. Daniel Klionsky, University of Michigan (USA), for kindly providing atg mutants and GFP-Atg8 fusion construction and to Prof. Andrea Harand, Federal University of Pernambuco (UFPE, Brazil) for the use of fluorescence microscopy. Chemical analyses were performed at the Analytical Centre of the Department of Fundamental Chemistry (UFPE, Brazil). This work was supported with grants from the Brazilian funding agencies FACEPE (project APQ-1452-2.01/10) and CNPq (project 472533/2013-4) and by the research support program of the Federal University of Pernambuco (project 23076.021846/2012-47). MRX and MGQ received master and PhD scholarship supports from CAPES agency and MMOL/LSS received PhD scholarship support from FACEPE agency.
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Conflict of interest
All authors declare that they have no conflict of interest.
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